Mangi M H, Mufti G J
Department of Haematological Medicine, King's College School of Medicine and Dentistry, London, UK.
Blood. 1992 Jan 1;79(1):198-205.
Material from 63 cases with primary myelodysplastic syndromes (P-MDS) (French-American-British [FAB] types: refractory anemia [RA] = 21; RA with ring sideroblasts [RARS] = 8; RA with excess of blasts (RAEB) = 10; RAEB in transformation (RAEBt) = 6; chronic myelomonocytic leukemia [CMML] = 10 and unclassifiable = 8, ie, bone marrow aspiration was inadequate and stringent FAB criteria were not applicable) was analyzed for bone marrow histologic and immunohistochemical patterns. Standard Giemsa, hematoxylin and eosin (H&E) and reticulin stains were used for morphologic assessment. To identify the cell lineage precisely, chloroacetate esterase staining and an indirect immunoperoxidase technique using mouse monoclonal antibodies CD15, CD68, HLA-DR, and rabbit polyclonal CD3 and UEA-1 (lectin) was developed on formalin-fixed paraffin embedded bone marrow biopsies (BMB). The immunohistochemical assessment permitted accurate identification of dysplastic features such as mononuclear and binuclear megakaryocytes, Pelger-Huet neutrophils, and binuclear erythroblasts. Additional bone marrow histologic and immunohistochemical features observed were heterogeneity of immunohistochemical staining in various cell lineages, megakaryocytic emperipolesis, alteration of bone marrow microarchitecture, intravascular clusters of hematopoietic cells, and the types of benign lymphoid aggregates. The nature of abnormally localized immature precursors (ALIP) was discerned. Three types of clusters of immature cells were found that were difficult to distinguish on Giemsa and H&E morphology, these were erythroid aggregates (n = 18); megakaryocytic aggregates (n = 4), and immature granulocytic and monocytic aggregates (n = 32). The bone marrow histologic and immunohistologic patterns permitted the identification of four groups of clinical relevance: Group 1, cases with predominant erythroid hyperplasia and without ALIP (n = 15); group 2, cases with prominent myeloid hyperplasia and presence of ALIP (n = 32); group 3, cases with hypoplastic MDS (n = 10); and group 4, cases with hyperfibrotic MDS (n = 6). Statistical analysis showed a significant difference in survival and leukemic transformation between groups 1, 2, 3, and 4, with cases in group 2 showing the worst prognosis with early death due to increased propensity to leukemic transformation and cytopenia-related complications (P less than .0001). We conclude that immunohistochemistry is feasible on routinely processed BMB and the information obtained is of diagnostic and prognostic importance in P-MDS. The phenotype of ALIP varies with the morphologic and histologic subtypes of MDS and the term should be reserved for cases in whom the clusters in the intertrabecular region are of myeloid (granulocytic and monocytic) lineage on immunohistochemistry.
对63例原发性骨髓增生异常综合征（P-MDS）患者的材料（法国-美国-英国[FAB]分型：难治性贫血[RA]=21例；环形铁粒幼细胞性难治性贫血[RARS]=8例；原始细胞增多的难治性贫血（RAEB）=10例；转变中的RAEB（RAEBt）=6例；慢性粒-单核细胞白血病[CMML]=10例，无法分类的=8例，即骨髓穿刺取材不足且严格的FAB标准不适用）进行骨髓组织学和免疫组织化学模式分析。采用标准吉姆萨、苏木精和伊红（H&E）及网硬蛋白染色进行形态学评估。为精确识别细胞系，在福尔马林固定石蜡包埋的骨髓活检组织（BMB）上开展了氯乙酸酯酶染色及使用小鼠单克隆抗体CD15、CD68、HLA-DR以及兔多克隆抗体CD3和UEA-1（凝集素）的间接免疫过氧化物酶技术。免疫组织化学评估可准确识别发育异常特征，如单核和双核巨核细胞、Pelger-Huet中性粒细胞以及双核成红细胞。观察到的其他骨髓组织学和免疫组织化学特征包括不同细胞系免疫组织化学染色的异质性、巨核细胞的血细胞吞噬现象、骨髓微结构改变、造血细胞血管内聚集以及良性淋巴样聚集的类型。辨别了异常定位的幼稚前体细胞（ALIP）的性质。发现了三种幼稚细胞聚集类型，在吉姆萨和H&E形态学上难以区分，分别为红系聚集（n=18）；巨核系聚集（n=4），以及幼稚粒系和单核系聚集（n=32）。骨髓组织学和免疫组织学模式可识别出四组具有临床意义的病例：第1组，以红系增生为主且无ALIP的病例（n=15）；第2组，有明显髓系增生且存在ALIP的病例（n=32）；第3组，低增生性MDS病例（n=10）；第4组，高纤维增生性MDS病例（n=6）。统计分析显示第1、2、3和4组之间在生存和白血病转化方面存在显著差异，第2组病例预后最差，因白血病转化倾向增加和血细胞减少相关并发症而早期死亡（P<0.0001）。我们得出结论，免疫组织化学在常规处理的BMB上是可行的，所获得的信息在P-MDS中具有诊断和预后重要性。ALIP的表型随MDS的形态学和组织学亚型而变化，该术语应仅用于免疫组织化学显示小梁间区域的聚集为髓系（粒系和单核系）细胞系的病例。
